Pain management using cryogenic remodeling

ABSTRACT

Medical devices, systems, and methods for pain management and other applications may apply cooling with at least one probe inserted through an exposed skin surface of skin. The cooling may remodel one or more target tissues so as to effect a desired change in composition of the target tissue and/or a change in its behavior, often to interfere with transmission of pain signals along sensory nerves. Alternative embodiments may interfere with the function of motor nerves, the function of contractile muscles, and/or some other tissue included in the contractile function chain so as to inhibit muscle contraction and thereby alleviate associated pain. In some embodiments, other sources of pain such as components of the spine (optionally including herniated disks) may be treated.

CROSS-REFERENCES TO RELATED

This application is a continuation of U.S. application Ser. No.13/615,059, filed Sep. 13, 2012, which is a continuation of U.S.application Ser. No. 12/271,013 filed Nov. 14, 2008, now U.S. Pat. No.8,298,216, which claims the benefit of U.S. Provisional Application No.60/987,992, filed Nov. 14, 2007; the full disclosures of which areincorporated herein by reference for all purposes.

BACKGROUND OF THE INVENTION

The present invention is directed to medical devices, systems, andmethods, particularly for those which employ cold for treatment of painin a patient. Embodiments of the invention include cryogenic coolingneedles that can be advanced through skin or other tissues to inhibitneural transmission of pain signals. Other embodiments may inhibitmuscle spasm induced pain. The cooling may be applied so that thepain-inhibiting remodeling relies on mechanisms other than ablation.

Therapeutic treatment of chronic or acute pain is among the most commonreasons patients seek medical care. Chronic pain may be particularlydisabling, and the cumulative economic impact of chronic pain is huge. Alarge portion of the population that is over the age of 65 may sufferfrom any of a variety of health issues which can predispose them tochronic or acute pain. An even greater portion of the nursing homepopulation may suffer from chronic pain.

Current treatments for chronic pain may include pharmaceuticalanalgesics and electrical neurostimulation. While both these techniquesmay provide some level of relief, they can have significant drawbacks.For example, pharmaceuticals may have a wide range of systemic sideeffects, including gastrointestinal bleeding, interactions with otherdrugs, and the like. Opiod analgesics can be addictive, and may also ofthemselves be debilitating. The analgesic effects provided bypharmaceuticals may be relatively transient, making themcost-prohibitive for the aging population that suffers from chronicpain. While neurostimulators may be useful for specific applications,they generally involve surgical implantation, an expensive which carriesits own risks, side effects, contraindications, on-going maintenanceissues, and the like.

Neurolysis is a technique for treating pain in which a nerve is damagedso that it can no longer transmit pain signals. The use of neurotoxins(such as botulinum toxin or BOTOX®) for neurolysis has received somesupport. Unfortunately, significant volumes of toxins may be used on aregular basis for effective neurolysis, and such use of toxins can havesignificant disadvantages. Alternative neurolysis techniques may involvethe use of thermal injury to the nerves via the application ofradiofrequency (“RF”) energy to achieve ablation, cryoablation, or thelike. While several of these alternative neurolysis approaches may avoidsystemic effects and/or prevent damage, additional improvements toneurolysis techniques would be desirable.

In general, it would be advantageous to provide improved devices,systems, and methods for management of chronic and/or acute pain. Suchimproved techniques may avoid or decrease the systemic effects oftoxin-based neurolysis and pharmaceutical approaches, while decreasingthe invasiveness and/or collateral tissue damage of at least some knownpain treatment techniques.

BRIEF SUMMARY OF THE INVENTION

The present invention generally provides improved medical devices,systems, and methods for treatment of pain and other applications.Embodiments of the present invention may apply cooling with at least oneprobe inserted through an exposed skin surface (and/or other tissueoverlying a nerve) of a patient. The cooling may remodel one or moretarget tissues so as to effect a desired change in composition of thetarget tissue and/or a change in its behavior. Exemplary embodimentswill interfere with transmission of pain signals along sensory nerves.Alternative embodiments may interfere with the function of motor nerves,the function of contractile muscles, and/or some other tissue includedin a contractile function chain so as to inhibit muscle contraction andthereby alleviate chronic or acute pain related to muscle activity. Insome embodiments, other sources of pain such as components of the spine(optionally including herniated disks) may be treated.

In a first aspect, the invention provides a method for treating painassociated with a nerve of a patient. The nerve underlies a tissue. Themethod comprises manually manipulating a body of a treatment apparatuswith a hand. The body supports a needle, and the body is manipulated soas to penetrate a sharpened distal end of the needle into the tissue tothermally couple the needle with the nerve. The body supports a coolingfluid source, and cooling fluid is transmitted from the source to theneedle so that the fluid cools the needle and the needle cools the nervesufficiently that pain is inhibited.

The cooling fluid may cool the needle to a needle temperature in atarget temperature range. The target temperature range may be determinedin response to a desired duration of pain inhibition. The needletemperature may, for example, be sufficiently warm to inhibit ablationof the nerve. The desired duration may optionally be permanent, and theneedle temperature may be suitable to induce apoptosis of the nerve.Apoptosis-inducing treatments will not necessarily be permanent, asrepair mechanisms may still limit the pain inhibiting duration.Nonetheless, apoptosis may enhance pain relief duration (for example, toprovide pain relief lasting a plurality of months) and/or the durationof other effects of the cooling when compared to alternative treatmentregimes. The desired duration may alternatively be less than permanent,for example, with the needle temperature being in a tissue stunningtemperature range so that the nerve is capable of transmitting painsignals after the tissue warms. Optionally, the needle may be insertedin or adjacent to an epidural space near a spinal channel. By thermallycoupling the needle to nerves within the spinal channel (and/orperipheral nerves branching from the spinal channel) cooling of theneedle may be used to inhibit pain transmission into or via the spinalchannel.

In the exemplary embodiment, the body comprises a self-contained,hand-held body so that no power, cooling fluid, or other material needbe transmitted from a stationary structure along a flexible tetherduring treatment. At least a portion of the cooling may optionally beperformed through an electrically insulating surface of the needle, withthe needle often also having an electrically conductive surface.Measurement of the nerve may be provided by an electromyographic (“EMG”)system coupled to the electrically conductive surface of the needle. Theneedle will often be used to penetrate a skin surface of the patientoverlying the nerve, and visible scar formation along the skin surfacemay be inhibited by limiting cooling along the needle proximally of thenerve. In some embodiments, a plurality of cooling cycles may be used totreat the nerve, with the probe being warmed or warm fluid beinginjected to speed thawing between the cooling cycles. In manyembodiments, a needle may be detached from the body and another needlemounted in its place. The other needle is then used to cool tissue withcooling fluid from the cooling source. The body (and cooling fluidsource) can be disposed of after treating only the one patient.Refilling of the cooling fluid source can be inhibited so as to preventuse of the system with another patient, for example, by configuring thecooling fluid path to release the lost gases through appropriatelyshaped vents rather than refill couplers or the like.

In another aspect, the invention provides a system for treating pain ofa patient. The pain is associated with a nerve of the patient, and thenerve underlies a tissue. A system comprises a body having a handle anda needle that is supported by the handle. The needle has a proximal endadjacent the body and a distal end. The distal end is sharpened forpenetrating distally into the tissue to thermally couple the needle withthe nerve using manipulation of the handle. The cooling fluid source ismounted to the body and is supported by the handle. The cooling fluidsource is coupled to the needle along a fluid path. A fluid flow controlsystem is coupled to the fluid path so that the fluid cools the needleand the needle effects cooling of the nerve to inhibit the pain.

In another aspect, the invention provides a system for treating pain ofa patient. The pain is associated with a nerve underlying a tissue ofthe patient. The system comprises a body having a handle and a needlethat is supported by the handle. The needle has a proximal end adjacentthe body and a distal end with a lumen extending between the proximaland distal ends. The distal end is sharpened for penetrating distallyinto the tissue so as to thermally couple the lumen with the nerve. Theneedle has a 16-gauge needle size or less. A cooling fluid source iscoupled to the lumen of the needle by a fluid path, and a fluid flowcontrol system coupled to the fluid path is configured to introduce coolfluid from the cooling fluid source, so that the vaporization of thefluid within the lumen effects cooling of the nerve to inhibit the pain.

The needle will often have a 22-gauge needle size or less, preferablyhaving a 26-gauge needle size or less. Multiple needles may optionallybe provided to enhance and/or widen a treatment volume, such as byproviding two (or alternatively more than two) parallel and laterallyoffset needles. The fluid flow control system may comprise a length ofsilica tubing disposed along the fluid flow control path between thecooling fluid source and the lumen. Such tubing may have a small, veryconsistent inner diameter that helps meter the fluid flow, allowing thetemperature to be effectively controlled by a simple pressure controlvalve disposed between the lumen and an exhaust.

In yet another aspect, the invention provides a method for treating painassociated with a component of a spine of a patient. The methodcomprises denervating at least a portion of the component, the at leasta portion implicated in the pain. The component may comprise, forexample, a disk of the patient, and the denervated portion may comprisean annulus fibrosus, a nucleus propulsus, and/or the like.Alternatively, herniation may be treated by modifying the collagenstructure of the disk to strengthen the disk wall.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is perspective view of a self-contained cryogenic pain treatmentprobe and system according to an embodiment of the invention;

FIG. 1B is a partially transparent perspective view of theself-contained probe of FIG. 1A, showing internal components of thecryogenic remodeling system and schematically illustrating replacementtreatment needles for use with the disposable probe;

FIG. 2 schematically illustrates components that may be included in thetreatment systems of FIGS. 1A and 1B;

FIG. 3 is a schematic cross-sectional view of an embodiment of a distalportion of the probe in the system of FIG. 1B, showing a replaceableneedle and a pressure relief valve;

FIG. 3A illustrates an exemplary fused silica cooling fluid supply tubefor use in the replaceable needle of FIG. 3;

FIG. 4 is a more detailed view of a replaceable needle assembly for usein the system of FIGS. 1A and 1B;

FIG. 5 is a flowchart schematically illustrating a method for treatmentusing the disposable cryogenic probe and system of FIG. 1B;

FIG. 6 is a schematic cross-sectional view showing an alternativeexemplary needle interface, along with adjacent structures of the needleassembly and probe body;

FIG. 7 is a partial cross-sectional view schematically illustrating acryogenic treatment probe in which cooling is performed at least in partthrough an insulating surface, and having an electrically conductivesurface for coupling to an electromyographic system to facilitatelocating a nerve;

FIG. 8 is a block diagram schematically illustrating tissue componentsincluded in a contractile chain;

FIGS. 9A-9C illustrate a method for positioning a pain treatment probein an epidural space; and

FIG. 10 illustrates component tissues of a spine and treatment of thosetissues with a cooling probe.

DETAILED DESCRIPTION OF THE INVENTION

Very generally, the present invention provides improved medical devices,systems, and methods, most often for the treatment of pain. Theinvention will find application in a variety of medical treatments anddiagnoses, particularly for pain management of patients suffering fromchronic or acute pain. Many embodiments employ cooling to remodel one ormore target tissues so as to effect a desired change in a composition ofthe target tissue, and/or a change in its behavior. For alleviation ofpain, treatments may target nerve tissue so as to interfere with thegeneration or transmission of sensory nerve signals associated with thepain. Other embodiments may target motor nerve tissue, muscles,neuromuscular junctions, connective tissue, or the like, so as toalleviate pain associated with contraction of a muscle.

Chronic pain that may be treated using embodiments of the invention mayinclude (but is not limited to) lower back pain, migraine headaches, andthe like. Sources of chronic pain that may be alleviated at least inpart via one or more aspects of the invention may be associated withherniated disks, muscle spasm or pinched nerves (in the back or anywherein the rest of the body), foot pain (such as plantar fascitis, plantarfibroma, neuromas, neuritis, bursitis, ingrown toenails, and the like);pain associated with malignant tumors, and the like. Applications inlower back and extremity pain may include use for patients sufferingfrom facet joint pain syndrome, pseudosciatica, intraspinous ligamentinjury, superior gluteal nerve entrapment, sacroiliac joint pain,cluneal neuralgia, peripheral neuropathy, and the like.

Acute pain that may be treated using embodiments of the inventioninclude (but is not limited to) post-surgical pain (such as painassociated with thoracotomy or inguinal hernia repair), pain associatedwith procedures where an epidural block, spinal block, or other regionalanalgesia might otherwise be employed (such as during pregnancy, labor,and delivery to inhibit pain transmission via the sensory nerves withoutthe use of drugs), and the like. Note that the ability to manage painwithout (or with less) pharmaceutical agents may allow pain relief foran extended period of time and/or when drug interactions are of concern,for example, to allow pain reduction during early labor and decrease thepotential for missing the window of time when an epidural can beadministered.

Cooling times, temperatures, cooling fluid vaporization pressures,cooling fluid characteristics, cooling cycle times, and/or the like maybe configured to provide a desired (often a selectable) efficacy time.Treatments at moderate temperatures (for example, at temperatures whichonly temporarily stun tissues but do not induce significant apoptosis ornecrosis) may have only short term muscle contraction or pain signaltransmission inhibiting effects. Other treatments may be longer lasting,optionally being permanent. Fibroblastic response-based efficacy may, insome embodiments, be self-limiting. Probe, applicator, and/or controllerdesigns may allow treatments with efficacy that is less dependent onoperator skill, thereby potentially allowing effective treatments to beapplied by persons with more limited skill and/or training throughautomated temperature and time control. In some embodiments, no foreignbodies and/or material need be injected into and/or left behind aftertreatment. Other embodiments may combine, for example, cooling withapplication of materials such as bioactive agents, warmed saline, or thelike, to limit injury and/or enhance remodeling efficacy. Someembodiments of treatments may combine cooling with pharmaceuticals, suchas a neurotoxin or the like. In some embodiments, no tissues need beremoved to achieve the desired therapeutic effect, although alternativeembodiments may combine cooling with tissue removal.

In many embodiments, much or all of the treatment system may be includedin a single hand-held apparatus. For example, a probe body in the formof a housing may contain a sealed cooling fluid cartridge havingsufficient cooling fluid for treatment of a single patient. The housingmay also contain a controller and battery, with the housing often beingnon-sterilizable and configured for disposal so as to limit capitalinvestment and facilitate treatments in Third-World environments.

Target tissue temperatures for temporarily disabling nerves, muscles,and associated tissues so as to provide a “stun” effect may be fairlymoderate, often being in a temperature range of from about 10° C. to −5°C. Such temperatures may not permanently disable the tissue structures,and may allow the tissues to return to normal function a relativelyshort time after warming. Using electromyographic systems, stimulation,or the like, a needle probe or other treatment device can be used toidentify a target tissue, or the candidate target tissues may be cooledto a stunned temperature range to verify efficacy. In some embodiments,apoptosis may subsequently be induced using treatment temperatures fromabout −1° C. to about −15° C., or in some cases from about −1° C. toabout −19° C. Apoptosis may optionally provide a permanent treatmentthat limits or avoids inflammation and mobilization of cellular repair.Colder temperatures may be applied to induce necrosis, which may berelatively long-lasting, and/or which may incite tissue healing responsethat eventually restores tissue function. Hence, the duration oftreatment efficacy may be selected and controlled, with coolingtemperatures, treatment times, and/or larger volume or selected patternsof target tissue determining the longevity of the treatment effects.Additional description of cryogenic cooling for treatment of cosmeticand other defects may be found in co-pending U.S. patent Ser. No.11/295,204, filed on Dec. 5, 2005, and entitled “Subdermal CryogenicRemodeling of Muscle, Nerves, Connective Tissue, and/or Adipose Tissue(Fat),” the full disclosure of which is incorporated herein byreference.

Referring now to FIGS. 1A and 1B, a system for cryogenic remodeling herecomprises a self-contained probe handpiece generally having a proximalend 12 and a distal end 14. A handpiece body or housing 16 has a sizeand shape suitable for supporting in a hand of a surgeon or other systemoperator. As can be seen most clearly in FIG. 1B, a cryogenic coolingfluid supply 18 and electrical power source 20 are found within housing16, along with a circuit 22 having a processor for controlling coolingapplied by self-contained system 10 in response to actuation of an input24. Some embodiments may, at least in part, be manually activated, suchas through the use of a manual supply valve and/or the like, so thatprocessors, electrical power supplies, and the like may be absent.

Extending distally from distal end 14 of housing 16 is atissue-penetrating cryogenic cooling probe 26. Probe 26 is thermallycoupled to a cooling fluid path extending from cooling fluid source 18,with the exemplary probe comprising a tubular body receiving at least aportion of the cooling fluid from the cooling fluid source therein. Theexemplary probe 26 comprises a 30 g needle having a sharpened distal endthat is axially sealed. Probe 26 may have an axial length between distalend 14 of housing 16 and the distal end of the needle of between about ½mm and 5 cm, preferably having a length from about 1 cm to about 3 cm.Such needles may comprise a stainless steel tube with an inner diameterof about 0.006 inches and an outer diameter of about 0.012 inches, whilealternative probes may comprise structures having outer diameters (orother lateral cross-sectional dimensions) from about 0.006 inches toabout 0.100 inches. Generally, needle probe 26 will comprise a 16 g orsmaller size needle, often comprising a 20 g needle or smaller,typically comprising a 25 g or smaller needle.

Addressing some of the components within housing 16, the exemplarycooling fluid supply 18 comprises a cartridge containing a liquid underpressure, with the liquid preferably having a boiling temperature of theless than 37° C. When the fluid is thermally coupled to thetissue-penetrating probe 26, and the probe is positioned within thepatient so that an outer surface of the probe is adjacent to a targettissue, the heat from the target tissue evaporates at least a portion ofthe liquid and the enthalpy of vaporization cools the target tissue. Avalve (not shown) may be disposed along the cooling fluid flow pathbetween cartridge 18 and probe 26, or along the cooling fluid path afterthe probe so as to limit the temperature, time, rate of temperaturechange, or other cooling characteristics. The valve will often bepowered electrically via power source 20, per the direction of processor22, but may at least in part be manually powered. The exemplary powersource 20 comprises a rechargeable or single-use battery.

The exemplary cooling fluid supply 18 comprises a single-use cartridge.Advantageously, the cartridge and cooling fluid therein may be storedand/or used at (or even above) room temperature. The cartridges may havea frangible seal or may be refillable, with the exemplary cartridgecontaining liquid N₂O. A variety of alternative cooling fluids mightalso be used, with exemplary cooling fluids including fluorocarbonrefrigerants and/or carbon dioxide. The quantity of cooling fluidcontained by cartridge 18 will typically be sufficient to treat at leasta significant region of a patient, but will often be less thansufficient to treat two or more patients. An exemplary liquid N₂Ocartridge might contain, for example, a quantity in a range from about 7g to about 30 g of liquid.

Processor 22 will typically comprise a programmable electronicmicroprocessor embodying machine readable computer code or programminginstructions for implementing one or more of the treatment methodsdescribed herein. The microprocessor will typically include or becoupled to a memory (such as a non-volatile memory, a flash memory, aread-only memory (“ROM”), a random access memory (“RAM”), or the like)storing the computer code and data to be used thereby, and/or arecording media (including a magnetic recording media such as a harddisk, a floppy disk, or the like; or an optical recording media such asa CD or DVD) may be provided. Suitable interface devices (such asdigital-to-analog or analog-to-digital converters, or the like) andinput/output devices (such as USB or serial I/O ports, wirelesscommunication cards, graphical display cards, and the like) may also beprovided. A wide variety of commercially available or specializedprocessor structures may be used in different embodiments, and suitableprocessors may make use of a wide variety of combinations of hardwareand/or hardware/software combinations. For example, processor 22 may beintegrated on a single processor board and may run a single program ormay make use of a plurality of boards running a number of differentprogram modules in a wide variety of alternative distributed dataprocessing or code architectures.

Referring now to FIG. 2, the flow of cryogenic cooling fluid from fluidsupply 18 is controlled by a supply valve 32. Supply valve may comprisean electrically actuated solenoid valve or the like operating inresponse to control signals from controller 22, and/or may comprise amanual valve. Exemplary supply valves may comprise structures suitablefor on/off valve operation, and may provide venting of the cooling fluidpath downstream of the valve when cooling flow is halted so as to limitresidual cryogenic fluid vaporization and cooling. More complex flowmodulating valve structures might also be used in other embodiments.

The cooling fluid from valve 32 flows through a lumen 34 of a coolingfluid supply tube 36. Supply tube 36 is, at least in part, disposedwithin a lumen 38 of needle 26, with the supply tube extending distallyfrom a proximal end 40 of the needle toward a distal end 42. Theexemplary supply tube 36 comprises a fused silica tubular structure 36 ahaving a polymer coating 36 b (see FIG. 3A) and extends in cantileverinto the needle lumen 38. Supply tube 36 may have an inner lumen with aneffective inner diameter 36 c of less than about 200 μm, the innerdiameter often being less than about 100 μm, and typically being lessthan about 40 μm. Exemplary embodiments of supply tube 36 have innerlumens of between about 15 and 50 μm, such as about 30 μm. An outerdiameter or size 36 d of supply tube 36 will typically be less thanabout 1000 μm, often being less than about 800 μm, with exemplaryembodiments being between about 60 and 150 μm, such as about 90 μm or105 μm. The tolerance of the inner lumen diameter of supply tubing 36will preferably be relatively tight, typically being about +/−10 μm ortighter, often being +/−5 μm or tighter, and ideally being +/−0.5 μm ortighter, as the small diameter supply tube may provide the majority of(or even substantially all of) the metering of the cooling fluid flowinto needle 26.

Though supply tubes 36 having outer jackets of polyimide (or othersuitable polymer materials) may bend within the surrounding needle lumen38, the supply tube should have sufficient strength to avoid collapsingor excessive blow back during injection of cooling fluid into theneedle. Polyimide coatings may also provide durability during assemblyand use, and the fused silica/polymer structures can handle pressures ofup to 100 kpsi. The relatively thin tubing wall and small outer size ofthe preferred supply tubes allows adequate space for vaporization of thenitrous oxide or other cooling fluid within the annular space betweenthe supply tube 36 and surrounding needle lumen 38. Inadequate space forvaporization might otherwise cause a buildup of liquid in that annularspace and inconsistent temperatures. Exemplary structures for use assupply tube 36 may include the flexible fused silica capillary tubingsold commercially by Polymicro Technologies, LLC of Phoenix, Ariz. undermodel names TSP, TSG, and TSU, optionally including model numbers TSP020090, TSP040105, and/or others.

Referring now to FIGS. 2 and 3, the cooling fluid injected into lumen 38of needle 26 will typically comprises liquid, though some gas may alsobe injected. At least some of the liquid vaporizes within needle 26, andthe enthalpy of vaporization cools the tissue engaged by the needle.Controlling a pressure of the gas/liquid mixture within needle 26substantially controls the temperature within lumen 38, and hence thetreatment temperature range of the tissue. A relatively simplemechanical pressure relief valve 46 may be used to control the pressurewithin the lumen of the needle, with the exemplary valve comprising avalve body 48 (here in the form of a ball bearing) urged against a valveseat 50 by a biasing spring 52.

During initiation of a cooling cycle, a large volume along the coolingfluid pathway between the exit from the supply tube and exit from thepressure relief valve 46 may cause excessive transients. In particular,a large volume in this area may result in initial temperatures that aresignificantly colder than a target and/or steady state temperature. Thiscan be problematic, particularly when (for example) the targettemperature is only slightly warmer than an undesirable effect inducingtemperature, such as when remodeling through apoptosis or the like whileseeking to inhibit necrosis. To limit such transients, the pressurerelief valve 46 may be integrated into a housing 54 supporting needle26, with the valve spring 52 being located outside the valve seat (andhence the pressure-control exit from pressure relief valve 46).Additionally, where needle 26 is included in a replaceable needleassembly 26A, pressure relief valve 46 is also located adjacent theinterface between the needle assembly and probe handpiece housing 54. Adetent 56 may be engaged by a spring supported catch to hold the needleassembly releasably in position, and the components of the needleassembly 26A (such as a brass or other metallic housing, a polyimidetubing 58, needle 26, and the like) may be affixed together usingadhesive. Alternatively, as illustrated in FIGS. 1B and 4, the needleassembly and handpiece housing may have corresponding threads formounting and replacement of the needle assembly. O-rings 60 can seal thecooling fluid pathway.

Additional aspects of the exemplary supply valves 32 can be understoodwith reference to FIGS. 2 and 3. In FIG. 3, the valve is shown in the“on” configuration, with O-rings 60 sealing either side of the coolingfluid flow path and the cooling fluid flowing around the moveable valvemember. When the valve 32 is in the “off” configuration, the coolingfluid flow path downstream of the valve is vented by channel 66. Ventingof the cooling fluid from the cooling fluid supply tube 36 when fluidflow is halted by supply valve 32 is advantageous to provide a rapidhalt to the cooling of needle 26.

Referring now to FIGS. 3 and 4, a wide variety of alternativeembodiments and refinements may be provided. Fluid supply 18 may beinitially opened for use by penetrating a frangible seal of thecartridge with a pierce point 70 (such as by tightening a threadedcartridge support coupled to housing 54), with the nitrous beingfiltered by a filter 72 before being transmitted further along thecooling fluid path. Suitable filters may have pore sizes of from about 6to about 25 μm, and may be available commercially from Porex of Georgia(or a variety of alternative suppliers), or may comprise a finestainless steel screen (such as those having a mesh size of 635 with0.0009″ wire and spacing between the wire edges of approximately0.0006″), or the like. A wide variety of epoxy or other adhesives 74 maybe used, and the replaceable needle housing 24A and other structuralcomponents may comprise a wide variety of metals or polymers, includingbrass or the like. Fins 76 may be included to help vaporize excesscooling liquid traveling proximally of the insertable length of needle26.

Very fine needles will typically be used to deliver to cooling at and/orbelow the surface of the skin. These needles can be damaged relativelyeasily if they strike a bone, or may otherwise be damaged or deformedbefore or during use. Fine needles will help inhibit damage to the skinduring insertion, but may not be suitable for repeated insertion fortreatment of numerous treatment sites or lesions of a particularpatient, or for sequential treatment of a large area of the patient.Hence, the structures shown in FIGS. 1B, 3, and 4 allow the use of probebodies 16, 54 with a plurality of sequentially replaceable needles.O-rings 60 help to isolate the cooling fluid supply flow (which may beat pressures of up to about 900 psi) from the exhaust gas (which may beat a controlled pressure in a range between about 50 and 400 psi,depending on the desired temperature). Exemplary O-rings may comprisehydrogenated Buna-N O-rings, or the like.

Referring now to FIG. 5, a method 100 facilitates treating a patientusing a cryogenic cooling system having a self-contained disposablehandpiece and replaceable needles such as those of FIG. 1B. Method 100generally begins with a determination 110 of the desired tissueremodeling and results, such as the alleviation of specific cosmeticwrinkles of the face, the inhibition of pain from a particular site, thealleviation of unsightly skin lesions or cosmetic defects from a regionof the face, or the like. Appropriate target tissues for treatment areidentified 112 (such as the subdermal muscles that induce the wrinkles,a tissue that transmits the pain signal, or the lesion-inducing infectedtissues), allowing a target treatment depth, target treatmenttemperature profile, or the like to be determined 114. An appropriateneedle assembly can then be mounted 116 to the handpiece, with theneedle assembly optionally having a needle length, skin surface coolingchamber, needle array, and/or other components suitable for treatment ofthe target tissues. Simpler systems may include only a single needletype, and/or a first needle assembly mounted to the handpiece.

Pressure, cooling, or both may be applied 118 to the skin surfaceadjacent the needle insertion site before, during, and/or afterinsertion 120 and cryogenic cooling 122 of the needle and associatedtarget tissue. The needle can then be retracted 124 from the targettissue. If the treatment is not complete 126 and the needle is not yetdull 128, pressure and/or cooling can be applied to the next needleinsertion location site 118, and the additional target tissue treated.However, as small gauge needles may dull after being inserted only a fewtimes into the skin, any needles that are dulled (or otherwisedetermined to be sufficiently used to warrant replacement, regardless ofwhether it is after a single insertion, 5 insertions, or the like)during the treatment may be replaced with a new needle 116 before thenext application of pressure/cooling 118, needle insertion 120, and/orthe like. Once the target tissues have been completely treated, or oncethe cooling supply cartridge included in the self-contained handpiece isdepleted, the used handpiece and needles can be disposed of 130.

A variety of target treatment temperatures, times, and cycles may beapplied to differing target tissues to as to achieve the desiredremodeling. For example, (as more fully described in patent applicationSer. No. 11/295,204, previously incorporated herein by reference)desired temperature ranges to temporarily and/or permanently disablemuscle, as well as protect the skin and surrounding tissues, may beindicated by Table II as follows:

TABLE II Temperature Skin Muscle/Fat 37° C. baseline baseline 25° C.cold sensation 18° C. reflex vasodilation of deep blood vessels 15° C.cold pain sensation 12° C. reduction of spasticity 10° C. very coldsensation reduction of chronic oedema Hunting response  5° C. painsensation  0° C. freezing point −1° C. Phase transition begins −2° C.minimal apoptosis −3° C. Peak phase transition −5° C. tissue damagemoderate apoptosis −8° C. Completion of phase transition −10° C. considerable apoptosis −15° C.  extensive apoptosis mild-moderatenecrosis −19° C.  adoptosis in some skeletal muscle tissues −40° C. extensive necrosis

To provide tissue remodeling with a desired or selected efficacyduration, tissue treatment temperatures may be employed per Table III asfollows:

TABLE III Cooled Temperature Range Time Effectiveness Purpose ≧0° C.Treatment lasts only while the Can be used to identify target needle isinserted into the tissues. target tissue. From 0° C. to −5° C. Oftenlasts days or weeks, and Temporary treatment. Can be target tissue canrepair itself. used to evaluate effectiveness Embodiments may last hoursof remodeling treatment on or days. skin surface shape or the like. From−5° C. to −15° C. Often lasts months to years; Long term, potentiallyand may be permanent. permanent cosmetic benefits. Limited musclerepair. Can be deployed in limited Embodiments may last weeks doses overto time to achieve to months. staged impact, controlling outcome andavoiding negative outcome. May be employed as the standard treatment.From −15° C. to −25° C. Often lasts weeks or months. May result inMid-term Muscle may repair itself via cosmetic benefits, and can besatellite cell mobilization. used where permanent effects Embodimentsmay last years. are not desired or to evaluate outcomes of potentiallypermanent dosing. Embodiments may provide permanent treatment.

There is a window of temperatures where apoptosis can be induced. Anapoptotic effect may be temporary, long-term (lasting at least weeks,months, or years) or even permanent. While necrotic effects may be longterm or even permanent, apoptosis may actually provide more long-lastingcosmetic benefits than necrosis. Apoptosis may exhibit anon-inflammatorycell death. Without inflammation, normal muscular healing processes maybe inhibited. Following many muscular injuries (including many injuriesinvolving necrosis), skeletal muscle satellite cells may be mobilized byinflammation. Without inflammation, such mobilization may be limited oravoided. Apoptotic cell death may reduce muscle mass and/or mayinterrupt the collagen and elastin connective chain. Temperature rangesthat generate a mixture of these apoptosis and necrosis may also providelong-lasting or permanent benefits. For the reduction of adipose tissue,a permanent effect may be advantageous. Surprisingly, both apoptosis andnecrosis may produce long-term or even permanent results in adiposetissues, since fat cells regenerate differently than muscle cells.

Referring now to FIG. 6, an exemplary interface 160 between a cryogeniccooling needle probe 162 and the associated probe body structure 164 areillustrated, along with adjacent portions of the needle, valve, probebody, and the like. Needle probe 162 is included in a needle assemblyhaving a needle hub 166 with a lumen containing a polyimide tube 168around a fused silica cooling fluid supply tube with its polyimidejacket 170. O-rings 172 seal in exhaust gas path 174 and inlet coolingfluid path 176, with the inlet path having a vent 178 to minimize run-oncooling when the cooling fluid supply is shut off by a valve 180, asgenerally described above. The valve is here actuated by a motor 182,while the exhaust gas pressure is controlled using a biasing spring andball valve 184 as described above. A hollow set screw 186 can be used toassemble and/or adjust the pressure relief valve, and a thermistor 188can be used to sense cooling gas flow.

Referring now to FIG. 7, cryogenic cooling probe 196 is inserted into atarget tissue TT and a flow of cryogenic cooling fluid is injected intothe needle as generally described above. A region 200 of target tissueTT is cooled sufficiently to freeze and effect the desired remodeling ofat least a portion of the target tissue. Rather than waiting for thefrozen tissue to thaw, in the embodiment of FIG. 7 a lubricious coating202 facilitates removal of the needle while at least a portion of thetarget tissue remains frozen. The lubricious coating may comprise amaterial having a thermal conductivity which is significantly less thanthat of the underlying probe structure 204. Coating 202 may have athickness which is significantly less than that of the underlying probestructure 204, limiting the total thermal insulation effect of thecoating, and/or an internal temperature of probe 196 may be reduced soas to provide the overall cooling treatment. Note that a small surface206 of probe 196 may be free of lubricious coating 202. Where theunderlying probe structure 204 comprises an electrical conductor such asstainless steel (or some alternative metal), and where coating 202comprises an electrical insulator, the uncovered portion 206 may be usedas an electrode for neurostimulation during positioning of probe 196 orthe like. Additionally, an EMG system 212 may be coupled to theelectrically conductive surface 206 via a coupler 214 (see FIG. 2).Coupler 214 will typically be accessible from the exposed probe bodywhen needle 26 is inserted into the patient, and EMG system 212 may beused for identifying and/or verifying the location of nerve 216 duringand/or after insertion of needle 196, depending on the configuration ofthe conductive surface 206 and the like.

Referring now to FIG. 8, in some embodiments remodeling of the tissuemay inhibit contraction of a muscle so as to mitigate pain associatedwith contraction or spasm. Remodeling a tissue included in a contractilefunction chain 230 may be used to effect a desired change in thecomposition of the treated tissue and/or a change in its behavior thatis sufficient to alleviate the pain. While this may involve a treatmentof the tissues of muscle 232 directly, treatments may also target nervetissues 234, neuromuscular junction tissues 236, connective tissues 238,and the like. Still further tissues may directly receive the treatment,for example, with treatments being directed to tissues of selected bloodvessels so as to induce hypoxia in muscle 232 or the like. Regardless ofthe specific component of contractile chain 230 which is treated, thetreatment will preferably inhibit contraction of muscle 232 which wouldotherwise induce pain.

Referring now to FIGS. 9A-C, techniques known for accessing the epiduralspace for introduction of pain-inhibiting compounds may be adapted forpositioning cooling needles similar to those described herein. Byproviding a needle with a through-lumen having an open distal port nearthe end of the needle, saline or other fluids can be injected duringneedle insertion and positioning. Resistance of the needle to insertionand/or a change in injection resistance indicates the port may bedisposed in the epidural space. The through-lumen may be disposed on thecooling needle concentrically or eccentrically relative to the coolingfluid supply path and/or the exhaust fluid path. A hypodermic syringe(or the like) used to provide fluid to the through lumen may then bereplaced by a body containing or coupled to a cryogenic fluid coolingsource, as can be understood with reference to FIGS. 1B, 3, and 4.Alternatively, a separate needle having a through-lumen may be used as aguide for insertion of the cooling needle, such as by advancing thecooling needle through the through-lumen or the like.

As can be understood with reference to FIG. 10, the cooling needle 26may be thermally coupled to a target nerve by positioning the needle inproximity to a spinal cord adjacent the epidural space, to a branchnerve from the spinal column in or adjacent a vertebral foramen to aherniated disk, or to another target neural and/or spinal tissue.Verification of positioning may be provided using an electro-myographicsystem (EMG) as described above, and/or positioning may optionally beguided using fluoroscopy, ultrasound imaging, magnetic resonance imaging(MRI), and/or other imaging modalities.

While exemplary embodiments have been described in some detail forclarity of understanding and by way of example, a number ofmodifications, changes, and adaptations may be implemented and/or willbe obvious to those as skilled in the art. Hence, the scope of thepresent invention is limited solely by the independent claims.

What is claimed is:
 1. A method for treating pain or spasm associatedwith a nerve of a patient, the nerve underlying a tissue, the methodcomprising: manually manipulating a body with a hand, the bodysupporting a needle, the body manipulated so as to penetrate a sharpeneddistal end of the needle into the tissue to thermally couple the needlewith the nerve, wherein the body supports a cooling fluid source;wherein the needle has a lumen extending distally toward the distal end,wherein a cooling fluid supply tube extends distally within the lumen ofthe needle, and wherein the manipulating of the body is performed sothat the cooling fluid supply tube extends distally of the skin surface;and transmitting cooling fluid from the source to the needle so that thefluid flows through the fluid supply tube distally of the skin surfaceand cools the needle, and so that the needle cools the nervesufficiently that the pain is inhibited.
 2. The method of claim 1,wherein the cooling fluid comprises a cryogenic cooling fluid andfurther comprising vaporizing at least a portion of the cryogeniccooling fluid within the lumen of the needle so that enthalpy ofvaporization cools a tissue region of the patient to a temperature indesired range so as to interfere with pain signal transmission along thenerve, the nerve comprising a sensory nerve and extending within theregion.
 3. The method of claim 2, wherein the region is separated fromand disposed distally of the skin surface.
 4. The method of claim 2,wherein the cooling fluid comprises N₂O.
 5. The method of claim 4,wherein the cooling fluid supply comprises a cartridge supported by thebody, and wherein the cartridge contains a quantity of liquid N₂Osufficient for cooling a plurality of tissue regions of the patient, andfurther comprising storing the liquid N₂O in the cartridge at roomtemperature.
 6. The method of claim 2, further comprising removing theneedle from the body and mounting another needle to the body, manuallymanipulating the body so as to advance the distal end of the otherneedle through the skin; and transmitting cooling fluid from the coolingfluid source to another fluid supply tube within the other needle, andvaporizing at least a portion of the cryogenic cooling fluid within thelumen of the other needle so as to cool another tissue region of thepatient to a temperature in the desired range.
 7. The method of claim 6,wherein the size of the needle is 16 gauge or smaller.
 8. The method ofclaim 2, wherein the cooling fluid supply tube within the needle has anouter diameter in a range between about 60 and 150 micrometers.
 9. Themethod of claim 2, wherein the cooling of the nerve within the region tothe temperature is sufficient to induce long-term inhibition of painsignal transmission along the nerve.
 10. The method of claim 9, whereinthe temperature is less than −19° C. and the cooling of the nerve doesnot induce permanent inhibition of signal transmission along the nerve.11. A system for treating pain associated with a nerve of a patient, thenerve underlying a skin surface tissue, the system comprising: a needlehaving a distal end, the needle having a lumen extending distally towardthe distal end; a body having an interface, the interface removablyreceiving the needle, the body having a handle configured for manuallymanipulating with a hand when the needle is on the interface so as toadvance the distal end of the needle through the skin surface and intothe tissue to an inserted position, the needle being thermally coupledwith the nerve in the inserted position; and a cooling fluid supply tubeextending distally within the lumen of the needle such that the coolingfluid supply tube extends distally of the skin surface when the needleis in the inserted position, the cooling fluid supply tube coupleablewith a cooling fluid source so that cooling fluid flows from the sourcethrough the fluid supply tube distally of the skin surface and cools theneedle, and so that the needle cools the nerve sufficiently that thepain is inhibited.
 12. The system of claim 11, the nerve comprising asensory nerve and extending within a tissue region of the patient,wherein the cooling fluid comprises a cryogenic cooling fluid, whereinthe cooling fluid supply tube and the lumen of the needle are includedin a cooling fluid flow path configured so that at least a portion ofthe cooling fluid vaporizes within the lumen of the needle, when theneedle is in the inserted position within the tissue region and thecooling fluid flows along the cooling fluid path, such that enthalpy ofvaporization cools the tissue region to a temperature in desired rangeto interfere with pain signal transmission along the nerve.
 13. Thesystem of claim 12, wherein the needle and cooling fluid supply tube areconfigured so that region is separated from and disposed distally of theskin surface.
 14. The system of claim 12, further comprising the coolingfluid supply, the cooling fluid comprising N₂O.
 15. The system of claim12, wherein the cooling fluid supply comprises a cartridge supported bythe body, and wherein the cartridge contains a quantity of liquid N₂Osufficient for cooling a plurality of tissue regions of the patient andis configured for storage of the liquid N₂O in the cartridge at roomtemperature.
 16. The system of claim 15, further comprising a pluralityof needles, each of the needles removably receivable by the interface soas to facilitate sequentially removal and replacement of the needles onthe body, each of the needles having an associated distal end, a lumenextending toward the distal end, and a cooling fluid supply tube, thebody configured to sequentially transmit portions of the quantity of thecooling fluid from the cooling fluid source to the fluid supply tubeassociated with the needle received by the interface of the body so thatat least a portion of the cryogenic cooling fluid vaporizes within theassociated lumen of the receive needle so as to cool an associatedtissue region of the patient to a temperature in the desired range. 17.The system of claim 16, wherein the size of the needles is 16 gauge orsmaller.
 18. The system of claim 17, wherein the cooling fluid supplytube within each needle has an outer diameter in a range between about60 and 150 micrometers.
 19. The system of claim 18, wherein the distalend of the needle comprises a sharpened distal end configured topenetrate the skin surface.